In:
The Journal of Immunology, The American Association of Immunologists, Vol. 208, No. 1_Supplement ( 2022-05-01), p. 50.39-50.39
Abstract:
Demodex mites are obligate commensal parasites of hair follicles (HF) in mammals. Normally asymptomatic, inflammatory outgrowth of mites can accompany malnutrition, immune dysfunction and aging, but mechanisms restricting Demodex outgrowth and pathogenesis are not defined. Here, we show that control over mite HF colonization of mice requires ILC2s, IL-13, and its receptor IL-4Ra, but not IL-4 or the adaptive immune system. Epithelial HF-associated ILC2s elaborate IL-13 that attenuates HF and epithelial cell proliferation at anagen onset; in their absence, Demodex colonization leads to increased epithelial proliferation and replacement of gene programs for repair by aberrant inflammatory programs leading to loss of barrier function and premature HF exhaustion over time. Humans with rhinophymatous acne rosacea, a nasal inflammatory condition associated with a high burden of Demodex, had increased HF inflammatory cells with decreased type 2 cytokines, consistent with the inverse relationship seen in mice. Our studies uncover a critical role for skin ILC2s and IL-13, which comprise an immune checkpoint necessary to sustain cutaneous integrity and restrict pathologic infestation by colonizing HF mites. This work was supported by the National Institutes of Health (AR007175 to R.R.R.G. and M.S.F, AR075880 to R.R.R.G, HL140868 to M.E.K., DK121476 to C.E.O., AI159229 to W.D., AR074556 to M.S.F., AI026918 and HL107202 to R.M.L.), Dermatology Foundation (R.R.R.G., M.S.F.), A.P. Giannini Foundation (R.R.R.G, M.E.K.), Robert Wood Johnson Foundation (R.R.R.G.), Howard Hughes Medical Institute (R.M.L.), University of California Tobacco-Related Disease Research Program (T29IP0554 to J.S.F.), and the Sandler Asthma Basic Research Center at the University of California San Francisco. R.E. Díaz was supported by NSF GRFP (#1650113). R.E. Díaz is a Howard Hughes Medical Institute Gilliam Fellow (#GT11377).
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.208.Supp.50.39
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2022
detail.hit.zdb_id:
1475085-5
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